The effect of various benzodiazepines (peripheral-type receptor ligand
s: Ro 5-4864, PK 11135; central-type receptor ligands: clonazepam, Ro
15-1788, Ro 15-4513; mixed type: diazepam) on the proliferation of est
rogen-induced rat pituitary prolactin-secreting tumor cells was studie
d in vitro. [H-3]thymidine incorporation into DNA was used as an index
of cell proliferation. It was found that tested peripheral- and mixed
-type benzodiazepine receptor ligands significantly suppressed the pit
uitary cell proliferation in a dose-dependent manner (10(-4)-10(-8) M)
. The inhibitory effect of Ro 5-4864 was reversed by 5 x 10(-3) M calc
ium chloride. On the other hand, central-type benzodiazepine receptor
ligands suppressed tumor cell proliferation only at the highest concen
tration studied (10(-4) M). Our results indicate that benzodiazepines
might exert an antiproliferative action on pituitary tumor cell growth
, and that this effect seems to be a calcium-dependent process.